SCL19A3 gene mutation with Leigh-like phenotype presentation: a potentially treatable disease
Bibliographic record
Abstract
A two-month-old boy presented with breastfeeding difficulty, hypoactivity, hyporeactivity, and seizures. Neuroimaging showed multiple areas of cytotoxic and vasogenic edema in the midbrain, cerebellum, basal ganglia, and brain hemispheres, with lactate peak ([ Figure 1 ]). Exome sequencing revealed a heterozygous mutation c.597dup (p.His200Serfs*25) in the SCL19A3 gene. Figure 1 Brain magnetic resonance imaging (MRI) scan at two months of age. Axial diffusion ( A , B ); fluid-attenuated inversion recovery (FLAIR) ( C ); apparent diffusion coefficient (ADC) map ( D , E ); and T2-weighted imaging ( F ). Symmetric areas of cytotoxic (red arrows) and vasogenic (asterisk) edema in the midbrain, superior vermis, subcortical white matter of the cerebral hemispheres, genu of the corpus callosum, internal capsules, and basal ganglia, mainly in the putamina and thalami. There are also some cystic changes in the occipital lobes (blue arrows). Magnetic resonance spectroscopy (MRS) ( G ) with intermediate TE (144 ms) showing the lactate inverted peaks at 1.3 ppm chemical shift (green arrow). The SCL19A3 gene encodes thiamine transporter-2. Mutations can result in thiamine metabolism dysfunction syndrome-2, and they can present as early as infantile Leigh-like syndrome,[ 1 ] a potentially treatable disease. This patient was submitted to thiamine and biotin replacement, but his evolution confirmed a poor prognosis ([ Figure 2 ]).[ 2 ] The poor outcome warrants genetic counseling for the families. Figure 2 Two-month follow-up after treatment with biotin and thiamine. Axial diffusion ( A ); FLAIR ( B ); T2- ( C ) and T1-weighted ( D ) multiplanar gradient-recalled (MPGR) imaging. Resolution of the areas with restriction diffusion and interval encephalomalacia and necrosis in the basal ganglia bilaterally, mainly in the thalami (arrows). There is diffuse cerebral atrophy and holohemispheric subdural hematomas (asterisk), due to stretching of the bridging veins. Authors' Contributions LFF: conceptualization, formal analysis, investigation, validation, visualization, writing of the original draft, and writing – review and editing; ECM: formal analysis, investigation, visualization, and writing – review & editing; TRN: formal analysis, funding acquisition, supervision, validation, and visualization; APA: investigation, supervision, validation, visualization, and writing of the original draft; MLD: validation, visualization, writing of the original draft, and writing – review and editing. Publication History Received: 26 May 2023 Accepted: 24 June 2023 Article published online: 13 October 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".